Patient Derived Organoids (PDOs) to Observe the Clinical Consistency of Personalized Neoadjuvant Therapy for Resectable Esophageal Squamous Cell Carcinoma
Design: This observational study will enroll patients diagnosed with resectable ESCC who undergo standard neoadjuvant therapy (chemotherapy +/- immunotherapy) before surgery. No treatments will be assigned by the study-therapy decisions remain in physicians' discretion based on standard care protocols. Participant Procedures: Patients will provide tissue samples (via endoscopy) used to grow PDO models and blood samples (optional) to study immune cell interactions with tumors. These samples will enable labs to test drug responses in vitro (lab-on-a-chip models) while patients proceed with their standard-of-care treatments and surgeries. Key Activities: Lab Work (non-invasive procedures post-endoscopy/surgery): PDO models grown from tumor tissue samples (culturing process) will mimic patients' tumors in miniature (preserving biological features). Drug sensitivity testing (chemotherapy agents like paclitaxel, platinum drugs and immunotherapies targeting PD-1/PD-L1 pathways\*\*) will assess how tumors respond (growth inhibition rates). Immune cell interactions (from blood samples) will model tumor-immune microenvironment responses to treatments (immunotherapy relevance). Clinical Follow-Up: Patients will undergo standard-of-care treatments (therapy decisions made independently) and regular monitoring post-treatment (survival follow-up every 3 months, adverse events tracked during therapy, clinical response evaluated per RECIST criteria). Duration: Study participation involves tissue/blood sample collection (during standard diagnostic procedures) followed by routine clinical care monitoring (treatment duration, post-surgery follow-up). Total study timeline spans March-December 2025 (1 year) with participant recruitment beginning February 2025. Ethical Considerations: Participants provide informed consent acknowledging optional blood sample collection (if needed) and understand study aims. Patient identifiers removed from samples/test results ensuring confidentiality (ethical compliance). No financial or treatment incentives-participation voluntary (patients retain autonomy) including withdrawal at any time (without affecting clinical care decisions). Study Significance: By bridging lab models with real-world treatment responses (PDOs validated against clinical outcomes), this research aims to develop personalized treatment strategies (precision oncology) reducing trial-and-error prescribing patterns (currently observed discrepancies in neo-adjuvant therapy responses among ESCC patients).
• Histologically confirmed esophageal squamous cell carcinoma via endoscopic biopsy.
• Primary tumor located in the thoracic esophagus (upper third: ≤25 cm from incisors; middle third: 25-30 cm; lower third: ≥30 cm).
• Clinical staging indicates resectable ESCC based on chest/abdominal enhanced CT, neck lymph node ultrasound, PET-CT/EUS: AJCC/UICC 8th Edition clinical stage excluding T4b, ≥6 lymph node metastases, ≥3 regional lymph node stations involved/metastatic disease (M1).
• Age: 18-75 years inclusive.
• ECOG performance status score of 0 or 1, with life expectancy ≥12 months.
• Adequate organ function: WBC \>4.0×10⁹/L, ANC ≥2.0×10⁹/L, platelets \>100×10⁹/L, hemoglobin \>90g/L; FEV1 ≥1.2L/FVC≥50%/DLCO≥50%; serum bilirubin ≤1.5×ULN; ALT/AST ≤1.5×ULN; SCr ≤120 µmol/L/Ccr ≥60 ml/min.
• Willingness and ability to provide informed consent, comply with follow-up requirements, and participate actively in drug sensitivity testing using PDO models.